CANMAT Depression Guidelines 2009.PDF

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Introduction

Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinicalguidelines for the management of major depressive disorder in adults

Sidney H. Kennedy a , , Raymond W. Lam b , Sagar V. Parikh a , Scott B. Patten c, Arun V. Ravindran aa University of Toronto, Canadab University of British Columbia, Canadac University of Calgary, Canada

a r t i c l e i n f o

Article history:Received 1 May 2009Accepted 23 June 2009Available online 13 August 2009

A working committee of the Canadian Network for Moodand Anxiety Treatments (CANMAT), a not-for-pro t scienti cand educational organization, met in 2008 to discuss theprocess and structure for revising the 2001 Canadian Guide-lines for the Management of Depressive Disorders that wasoriginally co-sponsored by CANMAT and the CanadianPsychiatric Association ( Kennedy and Lam, 2001 ). Thequestion answer format of the guidelines was retainedowing to ease-of-use by busy clinicians. The committeeupdated the original list of questions to include progress inthe eld. The draft question list was circulated amongstgroups of practitioners (psychiatrists and family physicians)for further suggestions.

A systematic literature search was conducted to identifyrelevant studies for each question via a computerized search,using appropriate key words, of electronic databases (PubMed,PsychInfo, Cochrane Library of Systematic Reviews and ClinicalTrials). Studies were also identi ed by cross-referencing of bibliographies, review of other major reports and guidelines,and feedback from experts. Published studies in English from January 1, 2000 to December 31, 2008 wereconsidered,with anemphasis on randomized controlled trials (RCTs) and meta-analyses. Information from the studies was extracted andsummary evidence tables created. These evidence tables areavailable on the CANMAT web site ( www.canmat.org ).

Levels of evidence were speci ed for recommendations,based on criteria from the2001 guidelinesand revisedto re ect

Journal of Affective Disorders 117 (2009) S1 S2

Corresponding author.E-mail address: [email protected] (S.H. Kennedy).

Table 1Criteria for Level of Evidence.

Level Criteria

1 At least 2 RCTs with adequate sample sizes, preferably placebo-controlled, and/or meta-analysis with narrow con dence intervals.

2 At least 1 RCT with adequate sample size and/or meta-analysiswith wide con dence intervals.

3 Non-randomized, controlled prospective studies or case seriesor high quality retrospective studies.

4 Expert opinion/consensus.

consensus opinions about quantitative reviews ( Liebermanetal., 2005 ) ( Table 1 ). It is important tonotethat theseLevels of Evidence do not assume positive or negative or equivocalresults; they merely represent the quality and nature of thestudies that have been conducted.

In addition, recommendations were gradedaccording toLineof Treatment, based on the criteria used for the 2001 guidelines(Table 2 ). A rst-line treatment represents a balance of ef cacy,tolerability and clinical support. Clinical support refers toapplication of expert opinion of the CANMAT committees toensure that evidence-supported interventions are realistic andapplicable for clinical practice, in order to enhance the utility of the guidance for clinicians. Therefore, treatments with higherlevels of evidence may be downgraded to lower Lines of Treatment due to clinical issues such as side effect or safetypro le. Second-line and third-line treatments are reserved forsituations where rst-line treatments are not indicated orcannot be used, or when rst-line treatments have not worked.

Manuscript drafts were circulated amongst committeemembers for discussion and consensus. Later drafts were thenreviewed by external content experts. Final manuscripts wereapproved by all co-authors. The guidelines process anddistribution were funded entirely by internal CANMAT funds;no external support was sought or received. All guidelinescommittee members disclosed potential con icts of interest.

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Contents lists available at ScienceDirect

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The revised guidelines are comprised of 5 sections:1) Classi cation, burden and principles of management;2) Psychotherapy alone or in combination with antidepres-sant medication; 3) Pharmacotherapy; 4) Neurostimulationtherapies; and 5) Complementary and alternative medicinetreatments. The scope of these guidelines encompasses themanagement of adults with unipolar major depressive

disorder (MDD). Guidelines for bipolar depression areincluded in the CANMAT guidelines for bipolar disorder(Yatham et al., 2009 ). Some questions include informationand summary recommendations for other special populations(children and adolescents, older age, pregnant women,medical comorbidity) but there are full guidelines availablethat address those groups.

CANMAT recognizes that much of the evidence is based onstudies using strict inclusion/exclusion criteria, intensive andfrequent follow up, short duration of treatment, etc., andtherefore may not be applicable to the average patient seen byclinicians. Hence, there are fewabsolute recommendations andthese guidelines should be viewed as guidance that must be

tailored to an individual patient, and not as standards of care.To be comprehensive, these guidelines encompass avarietyof treatments including psychotherapy, pharmacotherapy,neurostimulation and complementary and alternative medi-cine (CAM) treatments. There is, on balance, greater evidenceand clinical experience with traditional treatments (psy-chotherapy and pharmacotherapy) and few studies directlycomparing these with neurostimulation or CAM treatments.Therefore, rst-line psychotherapyor pharmacotherapy recom-mendationsusually should be consideredbefore neurostimula-tion or CAM treatments.

As these guidelines are primarily addressed to specialists(psychiatrists and other mental health professionals), the level

of detail may be greater than needed for primary carepractitioners; a shorter summary of these guidelines will bemade available for this group. The value of these guidelines tohelp de ne the best possible care for people with MDD willultimately be determined by the clinicians and patients whouse them.

Disclosures

SHK is on Speaker/Advisory Boards for, or has receivedresearch funds from: Advanced Neuromodulation SystemsInc, AstraZeneca, Biovail, Boehringer-Ingelheim, Brain CellsInc, Canadian Network for Mood and Anxiety Treatments, EliLilly, GlaxoSmithKline, Janssen-Ortho, Lundbeck, Merck Frost,Servier and Wyeth.

RWL is on Speaker/Advisory Boards for, or has receivedresearch funds from: Advanced Neuromodulation SystemsInc., AstraZeneca, BrainCells Inc., Biovail, Canadian Institutesof Health Research, Canadian Network for Mood and AnxietyTreatments, Canadian Psychiatric Research Foundation, EliLilly, Janssen, Litebook Company Ltd., Lundbeck, LundbeckInstitute, Mathematics of Informatics Technology andAdvanced Computing Systems, Michael Smith Foundationfor Health Research, Servier, Takeda, UBC Institute of MentalHealth/Coast Capital Savings, and Wyeth.

SVP is on Speaker/Advisory Boards for, or has receivedresearch funds from: Apotex, AstraZeneca, Biovail, BristolMyers Squibb, Canadian Network for Mood and AnxietyTreatments, GlaxoSmithKline, Janssen, Lilly, Lundbeck, Novar-tis, P zer, and Wyeth.

SBP is on Speaker/Advisory Boards for, or has receivedresearch funds from: Cipher Pharmaceuticals, CanadianInstitutes of Health Research, Canadian Network for Moodand Anxiety Treatments, Norlein Foundation, and Servier.

AVR is on Speaker/Advisory Boards for, or has receivedresearch funds from: AstraZeneca, Canadian Network for Moodand Anxiety Treatments, Cephalon, Eli Lilly, GlaxoSmithKline, Janssen-Ortho, Lundbeck, P zer, Roche, Servier and Wyeth.

AcknowledgementThe authors thank Dr. Maria Teresa Cruz Lourenco for the

preparation of literature searches and Ms. Niette Yeung foreditorial support.

References

Kennedy, S.H., Lam, R.W. (Eds.), 2001. Clinical guidelines for the treatment of depressive disorders: Can. J. Psychiatry, 46 Suppl. 1, pp. 1S 92S.

Lieberman, J.A., Greenhouse, J., Hamer, R.M., Krishnan, K.R., Nemeroff, C.B.,Sheehan, D.V., Thase, M.E., Keller, M.B., 2005. Comparing the effects of antidepressants: consensus guidelines for evaluating quantitative reviewsof antidepressant ef cacy. Neuropsychopharmacology 30, 445 460.

Yatham, L.N., Kennedy, S.H., Schaffer, A., Parikh, S.V., Beaulieu, S., O'Donovan, C.,McQueen,G., McIntyre, R.S., Sharma,V., Ravindran,A., Young,L.T.,Young,A.H.,Alda, M.,Milev, R.,Vieta, E.,Calabrese, J.R., Berk, M.,Ha,K.,Kapczinski, F., 2009.Canadian Network for Mood and Anxiety Treatments (CANMAT) andInternational Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder:Update 2009. Bipolar Disord. 11, 225 255.

Table 2Criteria for Lines of Treatment.

Line of treatment Criteria a

First-line Level 1 or Level 2 evidence, plus clinical supportSecond-line Level 3 evidence or higher, plus clinical supportThird-line Level 4 evidence or higher, plus clinical support

a Clinical support refers to application of expert opinion of the CANMAT

committees to ensure that evidence-supported interventions are realistic andapplicablefor clinicalpractice,in orderto enhancethe utilityof theguidance forclinicians. Therefore, treatments with higher levels of evidence may bedowngraded to lower Lines of Treatment due to clinical issues such as sideeffect or safety pro le.

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Commentary

CANMAT Guidelines for depression: Clear and user-friendly

Ian M. Anderson a , , Peter M. Haddad ba Professor of Psychiatry and Honorary Consultant Psychiatrist, School of Community Based Medicine, Neuroscience and Psychiatry Unit, University of Manchester,M13 9PT, UK b Consultant Psychiatrist and Honorary Senior Lecturer, Greater Manchester West Mental Health NHS Foundation Trust, Manchester, UK

Major depression in a common and disabling conditionacross the world. It presents many treatment challenges, notleast the high proportion of sufferers who do not present tohealth professionals or receive no treatment. Even whentreatment is received many individuals fail to achieveadequate response or subsequently relapse. Enabling accessto, and optimising, treatment is therefore important andguidelines provide one resource in trying to achieve this. Thenew guidelines for the Management of Depressive Disorder inAdults from the Canadian Network for Mood and AnxietyTreatments (CANMAT) updates the network's previousguidance published in 2001. The revised guidelines arepresented as ve stand-alone sections; 1) Classi cation,burden and principles of management; 2) Psychotherapyalone or in combination with antidepressant medication; 3)Pharmacotherapy; 4) Neurostimulation therapies; and 5)Complementary and alternative medicine treatments ( CAN-MAT, 2009) . Each of the ve sections has a brief abstract thatincludes a summary of the main results. The guidanceprimarily deals with adults but brief information is alsoprovided on treating several special populations includingchildren and adolescents, the elderly, pregnant women andthose with medical comorbidity.

There are now a considerable number of guidelinesavailable for the treatment of depression and many of these,like those from CANMAT, are now in their second or thirdrevisions/updates. Most guidelines now share key featuresincluding attempts to systematically review the evidence, theinvolvement of a guideline development group or consensusmeeting, the use of operationalised levels of evidence and areview process prior to nalisation. The CANMAT guidelineshave been developed by professionals and experts in the eldwithout explicit user or carer involvement (as is the usualpattern for guidelines from professional bodies) andaddressed to specialists (psychiatrists and other mental

health professionals). There is the promise of a less detailedsummary for primary care to follow. The lack of a universallyaccepted evidence grading system means that guidelinesgenerally adopt their own version; evidence grading isseductively simple in principle but dif cult in practice. TheCANMAT version of the Level of Evidence , referring to theavailability, not outcome, of evidence, does not specifyplacebo treatment as the comparator for assessment of primary ef cacy. The matching of evidence to rst, secondand third line recommendations for treatment is then largelydependent on expert opinion.

A major problem for depression treatment guidelines isthe amount of evidence to synthesise. The increasing fashionfor meta-analysis is therefore a blessing for guidelinedevelopers, but one that requires a health warning. Thequality of meta-analyses vary widely and vagaries of theprimary data, decision about inclusion criteria for studiestogether with the interpretation of equivocal results remindsus that that in the end it is a very human process as much artas science going into the nal picture. Without going back tooriginal data much depends on the quality of meta-analysesin the literature and it is possible to reach differentconclusions. To illustrate this, the CANMAT guidelinespropose light therapy as a rst line treatment for seasonalaffective disorder based on published meta-analysis, whereasthe consultation draft to update the National Institute forHealth and Clinical Excellence (NICE) depression guidelines,after going back to the primary data, concluded that therewere was insuf cient evidence to recommend light therapyonce poorer quality studies had been excluded ( NICE, 2009).

For the clinician consulting these guidelines perhaps themost obvious feature is in their presentation. The CANMATguidance uses a question-and-answer format with each of the

ve sections posing between 12 and 26 key questionsfollowedby a succinct answer, often in terms of rst-, second-and third-line treatment alternatives. In contrast otherguidelines, such as those from the British Association forPsychopharmacology (BAP, Anderson et al. 2008 ) and NICEguidance ( NICE, 2009), have a narrative structure with sub-


Corresponding author.E-mail address: [email protected] (I.M. Anderson).




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sections. Each format has its advantages and disadvantages.CANMAT's question-and-answer format is attractive for busyclinicians who want to dip in for an answer to a speci cclinical question. On the other hand a narrative structure maybe better suited to addressing clinical context, such as using astepped care approach or choice between treatments. Decid-ing what questions to include in a question and answerformat is a matter of opinion and will be in uenced by theintended audience. CANMAT's review of evidence is brief andreadable, but at times at the expense of being clear aboutproblems with the quality of evidence and the uncertaintiesin the data. An example is Section 3.3 that discusses thecomparative ef cacy of antidepressants but without ade-quately addressing the question of clinical importance,potential sponsorship in uence and methodology, all of which muddy the waters.

It is helpful that the CANMAT guidelines take a clinicalusefulness approach to some terminology, for exampledispensing with the differentiation between relapse andrecurrence on the basis that they cannot be reliablydistinguished. Consequently it considers two phases for thetreatment of depression, acute and maintenance, in contrastto the traditional three-phase Kupfer model (acute, continua-tion and maintenance treatment). Other useful simpli ca-tions of terminology are to use the general term add-on

treatments instead of augmentation and combination

(because of dif culties distinguishing between additionswith and without intrinsic antidepressant activity) and anemphasis on considering strategies for non- or incompleteresponse rather than treatment resistance . It is perhaps ashame that there isn't a more dimensional approach todepression and more tailoring of treatments to the level of severity, or consideration of persistent milder/subthreshold

depression.What about the details of the guidance itself? It isreassuring that there are few surprises when comparingthese to other available guidelines. TheCANMAT guidance hasthe current advantage of being amongst the most up-to-dateand is probably the rst guideline to consider the evidence forthe atypical antipsychotic, quetiapine, as a monotherapy forunipolar depression, in addition to an add-on treatment. It isalso always good to discover something new (at least to us)such as the use of the term nutriceuticals (in fact coined in

1989) to describe natural nutritional substances used as drugsand that there is Level 2 evidence for yoga as a treatment fordepression, even though this is probably through non-speci cmechanisms.

Overall the CANMATguideline fordepression is a welcomeaddition. Its modular design and question-and-answer formatmake the guideline user-friendly. The downside is that thesefeatures make it more dif cult to integrate treatments fromdifferent therapy areas and mayreduce their usefulness whenapplied in a clinical context. Nevertheless clinicians should

nd it relatively easy to nd key information. The broad scopeand avoidance of unnecessary jargon are further attractions.Given the move to develop different, and hopefully moreappealing, guideline formats (e.g. Malhi and Adams, 2009 ), auseful research question would be to what extent the formatof guidelines makes it more likely that clinicians read andapply them.

Declaration of interests

IA and PMH have received honoraria for consultancy and/or lecturing from the manufacturers of various drugs used inthe treatment of depressive illness including AstraZeneca, Eli-Lilly, Lundbeck and Servier as well as industry support toattend scienti c meetings. PMH has been a principalinvestigator in an antidepressant trial sponsored by Eli-Lilly.IA has received grants for investigator led research fromAstraZeneca.

References

Anderson, I.M., Ferrier, I.N., Baldwin, R.C., Cowen, P.J., Howard, L., Lewis, G.,Matthews, K., McAllister-Williams, R.H., Peveler, R.C., Scott, J., Tylee, A.,2008. Evidence-based guidelines for treating depressive disorders withantidepressants: a revision of the 200 0 British Association for Psycho-pharmacology guidelines. J. Psychopharmacol. 22, 343 396.

Canadian Network for Mood and Anxiety Treatments (CANMAT, 2009.Guidelines for the management of depressive disorder in adults. Journalof Affective Disorders.

Malhi, G.S., Adams,D., 2009. Areguidelines in need of CPR? Thedevelopmentof clinical practice recommendations (CPR). Acta Psychiatr. Scand. 119(Suppl. 439), 5 7.

National Institute for Health and Clinical Excellence (NICE) (2009). Depres-sion in adults (update): draft guideline consultation (http://www.nice.org.uk/guidance/index.jsp?action=folder&o=43325) .

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Research report

Canadian Network for Mood and Anxiety Treatments (CANMAT) ClinicalGuidelines for the Management of Major Depressive Disorder in Adults.I. Classi cation, Burden and Principles of ManagementScott B. Pattena , , Sidney H. Kennedyb , Raymond W. Lamc, Claire O'Donovand , Marie J. Filteaue ,Sagar V. Parikhb , Arun V. Ravindranba University of Calgary, Canadab University of Toronto, Canadac University of British Columbia, Canadad Dalhousie University, Canadae Universit Laval, Canada

a r t i c l e i n f o a b s t r a c t


Background: Major depressive disorder (MDD) is one of the most burdensome illnesses inCanada. The purpose of this introductory section of the 2009 revised CANMAT guidelines is toprovide de nitions of the depressive disorders (with an emphasis on MDD), summarizeCanadian data concerning their epidemiology and describe overarching principles of managingthese conditions. This section on Classi cation, Burden and Principles of Management is oneof 5 guideline articles in the 2009 CANMAT guidelines.Methods: The CANMAT guidelines are based on a question answer format to enhanceaccessibility to clinicians. An evidence-based format was used with updated systematicreviews of the literature and recommendations were graded according to the Level of Evidenceusing pre-de ned criteria. Lines of Treatment were identied based on criteria that includedevidence and expert clinical support.Results: Epidemiologic data indicate that MDD af icts 11% of Canadians at some time in theirlives, and approximately 4% during any given year. MDD has a detrimental impact on overallhealth, role functioning and quality of life. Detection of MDD, accurate diagnosis and provisionof evidence-based treatmentarechallenging tasks forboth cliniciansand for thehealthsystemsin which they work.Limitations: Epidemiologic and clinicaldata cannotbe seamlessly linked due toheterogeneity of syndromes within the population.Conclusions: In the eight years since the last CANMAT Guidelines for Treatment of DepressiveDisorders were published, progress has been made in understanding the epidemiology andtreatment of these disorders. Evidence supporting specic therapeutic interventions issummarized and evaluated in subsequent sections.

2009 Published by Elsevier B.V.

Keywords:Major Depressive Disorder

Canadian Network for Mood and AnxietyTreatments (CANMAT)Classi cationsPrinciple of managementBurdenPrevalence

Introduction

The Canadian Psychiatric Association and the CanadianNetwork for Mood and Anxiety Treatments (CANMAT), anot-for-pro t scienti c and educational organization,

collaborated on the publication in 2001 of evidence-based Canadian clinical guidelines for the treatment of depressive disorders (Kennedy and Lam, 2001). A revisionof these guidelines was undertaken by CANMAT in 20082009 to update the recommendations based on newevidence. The scope of these guidelines encompasses themanagement of adults with unipolar major depressivedisorder (MDD). This section on classication, burden and


Corresponding author.E-mail address: [email protected] (S.B. Patten).

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principles of treatment is one of 5 guideline articles. Thereare separate CANMAT guidelines for Bipolar Disorder(Yatham et al., 2009).

The current classi cation of depressive disorders is basedon the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition (DSM-IV; American Psychiatric Association,2000) or Recurrent Depressive Episodes in the ICD-10Classi cation of Mental and Behavioral Disorders (http://www.who.int/classi cations/icd/en/ ). In neither case arethese diagnoses linked to etiopathology. MDD is associatedwith a substantial health, psychosocial and nancial burdenand is increasingly recognized as a target for chronic diseasemanagement. While standardized diagnostic criteria areavailable, clinical assessment mustextend beyond applicationof these criteria. It is important to consider the short term andlong-term components of management and these will beexpanded upon in subsequent sections of the guidelines,dealing with psychotherapies, pharmacotherapies, neurosti-mulation therapies and complementary and alternativemedicines. The recommendations are presented as guidancefor clinicians who should consider them in context of individual patients, and not as standards of care.

Methods

The full methods have been described elsewhere (Kennedyet al, 2009-this issue) but, in summary, relevant Englishlanguage publications from January 1, 2000 to December31, 2008 were identi ed using computerized searches of electronic databases (PubMed, PsychInfo, Cochrane Registerof Clinical Trials), inspection of bibliographies, and review

of other guidelines and major reports. The previous questionanswer format has been retained based on feedback fromclinicians. Recommendations for each Line of Treatmentarebasedon theLevelofEvidenceandclinical support (Table1).

1.1. What is a depressive disorder?

The DSM-IV provides a general denition for mentaldisorder: a clinically signicant behavioral or psychologicalsyndrome or pattern that occurs in an individual and that isassociated with present distress or disability or with asigni cantly increased risk of suffering death, pain, disability,or an important loss of freedom. In keeping with thisde nition, depressive disorders are mental disorders that arecharacterized predominantly by depressive features.

The DSM-IV concept of a depressive disorder addsconsiderable speci city to otherwise non-speci c terminol-ogy such as depression which might otherwise imply adepressed (or lowered) mood, a normal response to loss (i.e.bereavement) or a maladaptive reaction to stress (i.e. anadjustment disorder with depressed mood). Depression canalso be conceptualized as a dimensionof symptom expressionquanti able using symptom rating scales. In clinical practice,depressive symptom ratings have an important role to play incase- nding (screening) and in monitoring outcomes.

1.2. How are depressive disorders classi ed?

The two most important depressive disordersare MDD andDysthymic Disorder. The essential feature of MDD is theoccurrence of one or more Major Depressive Episodes. In turn,Major Depressive Episodesarede nedasperiodslastingatleast2 weeks characterized either by depressed mood (most of theday, nearly every day) and/or markedly diminished interest orpleasure in all, or almost all, activities (most of the day, nearlyevery day). In total, during the same2-weekperiod, theremustbe ve or more symptoms drawn from the list presented inTable 2. Major Depressive Episodes are also the predominantform of mood disturbance in Bipolar Disorder. These disordersare not discussed further here because CANMAT has producedseparate Canadian guidelines for Bipolar Disorders (Yathamet al., 2009). Dysthymic Disorder is characterized by achronically depressed mood that occurs most of the day, moredays than not, for at least 2 years. While depressed mood ispresent there must be at least two additional depressivesymptoms. Treatment of Dysthymic Disorder is not a focus of

these guidelines. In addition to MDD, Bipolar Disorder andDysthymic Disorder, DSM-IV contains a category for depressiveepisodes caused by the use of, or withdrawal from, a drug:Substance-Induced Mood Disorder, with Depressive Features.DSM-IV also recognizes depression caused by the directphysiological consequences of a general medical condition:Mood Disorder Due to a General Medical Condition, withDepressive Features. Finally, DSM-IV contains a residualcategory called Depressive Disorder Not Otherwise Specied.

1.3. What are the important subtypes of major depressivedisorder and Dysthymic Disorder?

DSM-IV includes subtypes (speciers) that can be used tofurther describe the courseandcharacteristicsof MDD. If there is

Table 1Criteria for Level of Evidencea and Line of Treatment.b

Level Criteria1 At least 2 RCTs with adequate sample sizes,

preferably placebo-controlled, and/ormeta-analysis with narrow con dence intervals

2 At least 1 RCT with adequate sample size and/ormeta-analysis with wide con dence intervals.

3 Non-randomized, controlled prospective studiesor case series or high quality retrospective studies.


Line of Treatment CriteriaFirst-line Level 1 or Level 2 evidence, plus clinical supportcSecond-line Level 3 evidence or higher, plus clinical supportc

Third-line Level 4 evidence or higher, plus clinical supportca Note that Level 1 and 2 evidence refer specically to treatment studies in

which randomized comparisons are available. Recommendations involvingepidemiological or risk factors primarily arise from observational studies,hence the highest Level of Evidence is usually Level 3. Higher orderrecommendations (e.g., principles of care) reect higher level judgment of the strength of evidence from various data sources, and therefore areprimarily Level 4 evidence.

b A rst-line treatment represents a balance of ef cacy, tolerability andclinical support. Second-line and third-line treatments are reserved forsituations where rst-line treatments are not indicated or cannot be used, orwhen rst-line treatments have not worked.

c Clinical support refers to application of expert opinion of the CANMATcommittees to ensure that evidence-supported interventions are realistic inclinical practice. Therefore, treatments with higher levels of evidence may be

downgraded to lower Lines of Treatment due to clinical issues such as sideeffect or safety pro le.

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a current episode, these speci ers refer to this episode.Otherwise, they are applied to the most recent episode. Someof the speci ers refer to severity: major depressive episodes canbe classi ed as mild, moderate or severe. Within the severecategory, the disorder may or may not be characterized bypsychotic symptoms. Additional speciers refer to clinicalfeatures, as presented in Table 3. Speci ers can also be used todescribe partial or full remission of symptoms. Course speciers

for Dysthymic Disorder refer to early onset (before age 21), lateonset, and the presence of atypical features.

1.4. How common are depressive disorders?

The prevalence of depressive disorders is usually reportedon a lifetime or annual basis. Lifetime prevalence is theproportion of the population meeting diagnostic criteria for adisorder at any time during their lives prior to the time of assessment. Annual prevalence is the proportion meetingdiagnostic criteria during the preceding year. One monthprevalence is less commonly reported and represents theproportion meeting diagnostic criteria during the monthpreceding an assessment interview. Lifetime prevalence

estimates should be interpreted with caution. Measurementof lifetime prevalence using typical epidemiologic researchinstruments requires respondents to recall speci c symptomsthat may have occurred many years prior to the actualassessment interview. Long-term follow-up studies suggestthat such symptoms are often not recalled so that diagnosticinstruments may fail to detect prior episodes (Andrews et al.,1999). For this reason, available estimates of lifetime pre-valence are probably underestimates (Andrews et al., 2005).

While prevalence re ects the frequency of depressivedisorders in a population, it does not reect the risk of developing a disorder: incidence. Assessment of incidencerequires that a population at risk be identi ed (i.e. those who

Table 2DSM-IV criteria for a Major Depressive Episode.

Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either depressed mood or markedly diminished interest or pleasure.(1)Depressed mood most of theday,nearlyeveryday,as indicatedby either subjectivereport(e.g., feels sador empty) or observation made byothers(e.g., appearstearful). Note: In children and adolescents, can be irritable mood.(2) Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account orobservation made by others). Additional criteria are derived from the following symptoms:(3) Signi cant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearlyevery day. Note: In children, consider failure to make expected weight gains.(4) Insomnia or hypersomnia nearly every day(5) Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down)(6) Fatigue or loss of energy nearly every day(7) Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick)(8) Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others)(9) Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specic plan, or a suicide attempt or a specic plan for committingsuicideNote: Do not include symptoms that are clearly due to a general medical condition, or mood-incongruent delusions or hallucinations.

DSM-IV (American Psychiatric Association, 2000).

Table 4Prevalence studies of MDD in general populations.

Prevalence (%)

Location (study) Criteria Current/1 month 12 months LifetimeCanada DSM-IV 1.3 4.0 10.8Europe (ESEMeD) DSM-IV 3.9 12.8Germany DSM-IV 5.6 10.7 17.1Netherland (NEMESIS) DSM-III-R 2.7 5.8 15.4UK (NSPM) ICD-10 2.1USA (NCS-R) DSM-IV 6.6 16.2USA (NCS) DSM-III-R 4.9 17.1Australia DSM-IV 3.2Australia ICD-10 3.3 Japan DSM-III-R 1.2 2.9

Modi ed from Lam and Mok (2008).

Table 3DSM-IV-TR subtypes of MDD (Lam and Mok, 2008).

Subtype DSM-IV-TR

speci er

Key features

Melancholicdepression

With melancholicfeatures

Non-reactive mood, anhedonia,weight loss, guilt, psychomotorretardation or agitation,morning worsening of mood,early morning awakening andexcessive or inappropriate guilt.

Atypicaldepression

With atypicalfeatures

Reactive mood, over-sleeping,over-eating, leaden paralysis,interpersonal rejectionsensitivity

Psychotic (delusional)depression

With psychoticfeatures

Hallucinations or delusions

Catatonicdepression

With catatonicfeatures

Catalepsy (waxy exibility),catatonic excitement,negativism or mutism,mannerisms or stereotypes,echolalia or echopraxia(uncommon in clinical practice)

Chronicdepression

Chronic pattern Two years or more withfull criteria for MDE

Seasonal affectivedisorder (SAD)

Seasonal pattern Regular onset and remissionof depressive episodesduring a particular season(usually fall/winter onset)

Postpartumdepression (PPD)

Postpartumpattern

Onset of depressive episodewithin 4 weeks postpartum

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do not already have a depressive disorder), and that new casesemerging over a de ned time interval be identi ed. Also,prevalence estimates do not fully re ect the burden of depressivedisorders in the population.Disease burden dependsnot only on prevalence, but also on the amount of time spent inthe depressed state, the extent of associated disability and theassociated riskof prematuremortality. Burdenofdiseaseis mostoften quanti ed using composite parameters that combineinformation about prevalence, course, impairment and pre-mature mortality, for example the Disability Adjusted Life Year,orDALYused in theWorldHealth OrganizationGlobal Burdenof Disease Project (Ayuso-Mateos,2003;Murrayand Lopez,1996).

Early estimates of depressive disorder prevalence inCanada were derived from studies conducted in Edmonton(Bland et al., 1988a,b) and in the province of Ontario (Offordet al.,1996). National estimates becameavailable in 1994withthe rst interview cycle of the National Population HealthSurvey (NPHS) (Beaudet, 1996). The NPHS included a brief version of the major depression module of the CompositeInternational Diagnostic Interview (CIDI) (Kessler et al.,1998). As a longitudinal study, the NPHS also providednational incidence estimates (Beaudet, 1999; Patten, 2000;Patten and Lee, 2004). The rst national estimates of prevalence based on the full version of the CIDI interviewwere produced by the Canadian Community Health Survey,Mental Health and Wellbeing (CCHS 1.2) conducted byStatistics Canada in 2002 (Gravel and Bland, 2005). Table 4presents a summary of international prevalence estimates.

AccordingtotheCCHS 1.2, thelifetimeprevalenceofMDDinCanada is 10.8%. Annual and one month prevalence estimatesarisingfrom thissurvey were4.0% and1.3%respectively(Pattenet al., 2005b). These estimates are lower than in the US whereestimates of 16.2% lifetime and 6.6% annual prevalence werereported by Kessler et al. (2003). Canadian estimates moreclosely resemble recent European prevalence rates of 12.8%lifetime and 3.9% annual (Alonso et al., 2004). However, atelephone survey conducted jointly in Canada and the US didnot nd a difference in prevalence between the two countries(Vasiliadisetal.,2007).MDD has a higher prevalenceinwomenand in younger age groups, although this sex differencediminishes with increasing age in Canada (Patten et al.,2005a,b), a pattern that was previously reported in the UnitedKingdom(Bebbingtonet al.,1998). Accordingto NPHSdata, theoverall annual incidence of major depressive episodes is 3.1%(Patten and Lee, 2004). However, the incidence is higher inwomen and also tends to decline with age (Patten, 2000).

The CCHS 1.2 did not assess the prevalence of DysthymicDisorder, so national Canadian prevalence estimates are notavailable. The Edmonton study, which used DSM-III diagnos-tic criteria, reported 3.7% lifetime prevalence (Bland et al.,1988a,b), closely resemblingrecent European estimatesbasedon DSM-IV criteria, 4.1% lifetime (Alonso et al., 2004).Notably, the annual European prevalence was 1.1%, whichalso resembled the 0.8% annual prevalence estimate from theMental Health Supplement of the Ontario Health Survey,based on DSM-III-R criteria (Offord et al., 1996).

1.5. What is the long-term course of MDD?

In the CCHS 1.2, the reported duration of initial MajorDepressive Episodes was 2 weeks in 16% of episodes and one

month or less in 30% of episodes (Patten, 2006). At the otherextreme,13.7% of the subjects reported that their rst episodelasted 5 years or longer. The percentage of respondentsaccording to episode duration among those experiencing apast year major depressive episode is shown in Table 5.Mathematical modeling studies provide an explanation forthese results: the probability of recovery appears to declinewith increasingepisode duration (Patten and Lee, 2004). Meanepisode duration in the NPHS was 17 weeks (Patten and Lee,2004), but the mean duration obscures both the brief nature of some episodes and the protracted nature of others. Prevalenceis a product of incidence and duration, such that reducing theduration of episodes (for example, through treatment), in theabsence of other changes, will reduce the prevalence in thepopulation. Unfortunately, despite recent increases in treat-ment provision (Patten and Beck, 2004), a reduction inprevalence has not yet been discernable in those countrieswhere before after comparisons have been feasible (Brughaet al., 2004; Kessler et al., 2005). Many new-onset episodesoccurring in the general population are brief, but longerepisodes accumulate to a greater extent and predominate asprevalent cases in the population (Patten, 2006; Patten, 2007).

The Netherlands Mental Health Survey and Incidence Study(NEMESIS) provides importantdataon thelongitudinal courseof DSM-III-R dened MDD. This study retrospectively assessedepisode duration in community residents with new-onsetepisodes. Consistent with Canadian data, a sizable proportion of episodes were brief: 50%of episodes recoveredwithin 3 months.However, the recovery rate attened over time, and the authorsestimated that approximately 20% would have chronic episodespersisting longer than 24 months (Spijker et al., 2002).

MDD is often a recurrent condition. In the CCHS 1.2,respondents with lifetime MDD reported a single episode56.0% of the time, 2 episodes 28.6% of the time and 3 or morelifetime episodes 15.4% of the time (CCHS 1.2, Public UseMicrodata File). Given the potential role of recall bias (seeabove), it is likely that these are underestimates of thefrequency of recurrent episodes.

1.6. What is the impact of depressive disorders on population health?

6.1. How substantial is the disease burden associated with MDD?According to the Global Burden of Disease Study, MDD is

one of the world's leading causes of disability (Murray andLopez, 1996; The World Health Report 2001, 2001). Because

cognitive symptoms are prominent, the ongoing transition toa knowledge-basedeconomyis expected to further magnify theimpact of MDD on occupational functioning (The StandingSenate Committee on Social Affairs Science and Technology,2006). Depressive disorders impactsocietypartiallyby increas-ing suicide risk. In a study of 102 suicides in New Brunswick,

Table 5Number of weeks depressed (past year) in CCHS 1.2 respondents with past-year Major Depressive Episodes.

b 6 weeks 22.1%7 to 12 weeks 20.8%13 to 26 weeks 29.2%27 to 52 weeks 27.9%

Canadian Community Health Survey 1.2, Public Use Microdata File.



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almost 70% of victims had an affective disorder, usuallycomorbid with addictive or personality disorders (Seguinet al., 2006). Data from NEMESIS demonstrated that comorbidanxiety disorders amplify the risk of suicide attempt inindividuals with mood disorders (Sareen et al., 2005). Depres-sive disorders also have a major impact on qualityof life (QOL).In a study of QOL impairment in depressive and anxietydisorders, 63% of respondents with MDD had severe impair-ment in QOL, while85% of those with double depression (MDDand Dysthymic Disorder) and 56% of those with DysthymicDisorder had QOL impairment in the severe range (Rapaportet al., 2005).

1.7. What is the occupational impact?Depression profoundly affects occupational functioning,

both through absenteeism and presenteeism (loss of produc-tivity while attending work when unwell) (Sanderson et al.,2007). A longitudinal study found that depressed workershad signi cantly greater performance de cits than controlworkers (who had rheumatoid arthritis) with regard toperforming mental interpersonal tasks, time management,output tasks and physical tasks (Adler et al., 2006). Even after18 months of follow-up, clinical improvement did not resultin full recovery of job performance.

In a comparison of 6 depressed-at work and depressed-not at work populations, the depressed workers were morelikely to be young, better educated, white collar and of betteroverall health status than the non-working depressed group(Elinson et al., 2004). Depressed employees are also morelikely to become unemployed or miss time at work thanphysically ill employees (Hoge et al., 2002). When depressedworkers were compared to controls and workers withrheumatoid arthritis, the depressed employees becameunemployed ve times more frequently than the other 2groups (Lerner et al., 2004).

1.8. What is the impact of MDD on other functional domains?While occupational impairment has received the most

attention, depressive disorders also negatively affect func-tioning in non-occupational tasks. In fact, the NationalComorbidity Survey Replication study in the US found thatrole impairment in people with MDD was lowest in theoccupational domain and highest in the social domain(Kessler et al., 2003). In this survey, 59.3% of respondentswith past-year major depressive episodes reported severe orvery severe role impairment. Depression in women may also

have a negative effect on the development of their childrenand on familydynamics (Toney, 2007). Treatment of maternaldepression to remission in the STAR*D child study wasassociated with decreased psychiatric symptoms andimproved functioning in the offspring (Pilowsky et al.,2008). There is also evidence of increased consultation fordevelopmental and behavioral problems in the children of fathers whomeet criteria for majordepressive disorder (Daveet al., 2009). Such intergenerational effects may magnify theimpactof depression onpopulation health (Ramchandani andStein, 2003).

1.9. What is the impact of MDD on physical health?

MDD or depressive symptoms can negatively affectphysical health by reducing adherence to medical treatment

(Ciechanowski et al., 2000), reducing participation in pre-ventive activities (Aro et al., 1999), and altering risk factorssuch as obesity (McIntyre et al., 2006), smoking (Murphyet al., 2003) and sedentary lifestyles (van Gool et al., 2003).Depressed patients with or without diabetes have a higherincidence of obesity, metabolic disorders, higher insulinresistance, decreasedheart ratevariability andarteriosclerosis(Linetal.,2004). There is evidence from Saskatchewan Healthdata, that depressive disorders increase the risk of Type IIdiabetes (Brown et al., 2005). A growing body of evidencesuggests that MDD is also associated with immune dysfunc-tion (Corcos et al., 2002; Kop et al., 2002; Musselman et al.,2001; Penninx et al., 2003), and, in the case of recurrent MDD,with coronary and aortic calci cation in middle aged women(Agatisa et al., 2005). Depression is increasingly recognized asan independent risk factor for cardiovascular disease and anindependent predictor of mortality (Kop, 2003; Taylor et al.,2005;Wassertheil-Smoller et al.,2004;Writing committeeforthe ENRICHED investigators, 2003). Statistics Canada recentlyreported MDD to be predictive of new-onset heart disease inthe Canadian general population (Gilmour, 2008) and aScience Advisory Statement by the American Heart Associa-tion (endorsed by the American Psychiatric Association)recommended routine screening for depression in patientswith coronary heart disease (Lichtman et al., 2008). In addi-tion to these speci c examples, MDD appears to be associatedwith a general increase in chronic disease incidence (Pattenet al., 2008) and there is a joint effect of depression and thesechronic diseaseson functionaldisability (Schmitzetal.,2007).

While there has been much interest in the relationshipbetween MDD and chronic medical conditions such as heartdisease and diabetes, the conditions most strongly associatedwith MDD in the Canadian population are neurologicalconditions and conditions related to pain and in ammation(Table 6).

1.10. How do patients with MDD typically present inclinical practice?

Depressive disorders, as currently de ned by DSM-IV, arelargely symptom-based diagnostic entities. These disordersare associated with a very broad range of clinical presenta-tions,which must be understood in a biopsychosocial context.MDD canpresent at any agebut thepeak prevalence occurs inthose between the ages of 15 and 45 years (Patten et al.,2005b). Consequently, MDD has a disproportionately largeimpact on education, work productivity, relationships and

Table 6Medical conditions strongly associated with MDD in the Canadianpopulation.

Medical condition Odds ratio Medical condition Odds ratioEmphysema/COPD 2.7 Asthma 1.9Migraine 2.6 Stroke 1.7Multiple sclerosis 2.3 Thyroid disease 1.4Back problems 2.3 Diabetes 1.4Cancer 2.3 Heart disease 1.4Epilepsy 2.0

Estimates derive from the Canadian Community.Health Survey 1.1, Patten et al. (2005a).

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bothantidepressantmedicationsandpsychotherapy, (3)case-management in a collaborative context with stepped careoptions, (4) patient education about depression and self-management of depression and (5) process measurementsuch as monitoring of the timeliness and quality of care inaddition to measurementof symptomatic outcomein patients(KatesandMach,2007). A systematic reviewof10 high qualityrandomized controlled trials found robust evidence of the effectiveness of disease management for depression(Neumeyer-Gromen et al., 2004).

In the Canadian context, most treatment for depressivedisorders occurs in fee for service primary care practices,where disease management strategies are challenging toimplement. For example, fee for service funding arrange-ments do not generally provide support for case-manage-ment, which is a component of most disease managementstrategies. This situation may change in the future asprimary care reform leads to a greater emphasis on chronicdisease management. Nevertheless, collaborative care mod-els have been a focus of interest in Canada for many years(Kates, 2002). When shared or collaborative care arrange-ments are in place, the professionals involved must main-tain a clear awareness of their responsibilities within thosearrangements.

1.12. What are the phases of treatment?

Forheuristicpurposes, thetreatmentof MDDcan be dividedinto two phases: acute and maintenance (Table 9). The aim of acute treatment is to eliminate symptoms of depression andrestore psychosocial functioning. The aim of maintenancetreatment is to ensure a return to baseline function and qualityof life and to prevent recurrence of symptoms.

1.13. What are the basic principles of treatment?

Although approaches to management differ depending onthe context of care delivery, many of the basic principlesremain the same. Trends in collaborative MDD managementthat incorporate stepped care and disease managementhave common elements, most of which (the exception beingcase-management) are applicable to other treatment settings(see Table 10). These elements include systematic monitoring

of patient outcomes, treatment decisions that are evidence-based and responsive to therapeutic goals. The systematicprogression through available treatment options is consistentwith the CANMAT concept of Lines of Treatment which areelaborated in subsequent sections of these guidelines.Because MDD in itself may reduce treatment adherence, thisshould be discussed at an early stage and should bemonitored frequently during treatment in an open manner(Trivedi et al., 2007).

1.14. What are the goals of acute treatment?

The target goal for acute treatment should be remission: aresolution of depressive symptoms. Response to treatment(a reduction in symptom levels) is not an adequate outcomebecause residual depressive symptoms are risk factors forrelapse and negative predictors of long-term outcome(McIntyre and O'Donovan, 2004). Monitoring of symptomlevels during treatment is an essential metric of outcome.Outcome assessment can be conducted using validatedinterviewer-rated scales, e.g., the Hamilton Depression RatingScale (HDRS, Hamilton, 1960) or the Montgomery sbergDepression Rating Scale (MADRS, Montgomery and sberg,

1979). A seven-item version of the HDRS is a suitable tool forclinical practice because of its brevity and validity (McIntyreet al., 2002). Busy clinicians also may nd that the self-reportscales listed in Table 8 are ef cient tools to monitor progressand outcome. Response is usually dened as N 50% reductionin scores on these scales, while remission is dened as a scorewithin the normal range.

1.15. What are the goals of maintenance treatment?

The terms relapse (return of symptoms during a currentepisode)and recurrence (return of symptoms owing to a new

episode) are not functionally useful because there are nomethods to determine when an episode ends. Hence, oncepatients are treated in the acute phase and are well (i.e., insymptom remission), the critical questions are: how can theystay well and how long do treatments need to be maintained?The goals of this maintenance phase include resolving anyresidual symptoms, treating comorbid conditions, returningto full pre-morbid functioning and preventing return of symptoms (Table 10), Clinicians should focus on healthy lifestrategies, personality vulnerabilities, long-term self-manage-ment and clinical strategies to reduce recurrence (Rafanellietal., 2007). Continuedpharmacologic andnon-pharmacologictreatments have a role in the prevention of recurrence:

supporting evidence is evaluated in subsequent sections of these guidelines.

Table 9Phases of treatment for MDD.

Treatmentphase

Duration Goals Activities

Acute 8 12 weeks Remission of symptoms

Establish therapeuticalliance

Restore function Educate Select and use

treatment(s) Monitor progress

Maintenance 6 24 months,or longer

Return to fullfunction andquality of life

Educate Rehabilitate

Prevention of recurrence

Treat comorbidities Monitor for recurrence

Table 10Chronic disease management strategiesa for MDD.

Active efforts to detect depressionDelivery of evidence-based carePatient education about depressionProcess measurement and systematic outcome assessment

a Adapted from Kates and Mach, 2007.

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3. Conclusion

Depressive disorders are among the most common andburdensome conditions af icting the Canadian population.Evidence-based management can reduce their burden inaf icted individuals and ultimately in society as a whole. Bysummarizing an updated evidence base, the aim of theserevised CANMAT guidelines is to link the best availableevidence to the best possible care of depressed patients.

Con ict of interestNo con ict declared.

Role of funding sourcesThese guidelines were entirely funded with funding from the Canadian

Network for Mood and Anxiety Treatments; no external funds were sought orreceived.

SBPis on Speaker/AdvisoryBoards for, or hasreceived researchfunds from:Cipher Pharmaceuticals, Canadian Institutes of Health Research, CanadianNetwork for Mood and Anxiety Treatments, Norlein Foundation, and Servier.

SHK is on Speaker/Advisory Boards for, or has received research fundsfrom: Advanced Neuromodulation Systems Inc., AstraZeneca, Biovail,Boehringer-Ingelheim, Brain Cells Inc., Canadian Network for Mood andAnxiety Treatments, Eli Lilly, GlaxoSmithKline, Janssen-Ortho, Lundbeck,Lundbeck Institute, Merck Frost, Servier and Wyeth.

RWL is on Speaker/Advisory Boards for, or has received research fundsfrom: Advanced Neuromodulation Systems Inc., AstraZeneca, BrainCells Inc.,Biovail,Canadian Institutes ofHealthResearch, CanadianNetwork forMood andAnxiety Treatments, Canadian Psychiatric Research Foundation, Eli Lilly, Janssen, Litebook Company Ltd., Lundbeck, Lundbeck Institute, Mathematicsof Informatics Technology and Advanced Computing Systems, Michael SmithFoundation forHealthResearch,Servier, Takeda,UBC Institute ofMental Health/Coast Capital Savings, and Wyeth.

CO is on Speaker/Advisory Boards for, or has received research funds fromBiovail Inc., Wyeth, Servier and Astra Zeneca.

MJF is on Speaker/Advisory Boards for, or has received research fundsfrom: AstraZeneca, Biovail, Bristol-Myers-Squibb, Canadian Network forMood and Anxiety Treatments, Eli Lilly, Janssen Ortho, Lundbeck, Pzer,Servier, and Wyeth.

SVPis on Speaker/AdvisoryBoards for, orhas receivedresearch funds from:Apotex,AstraZeneca, Biovail,BristolMyers Squibb,CanadianNetwork forMoodand Anxiety Treatments, GlaxoSmithKline, Janssen, Lilly, Lundbeck, Novartis,P zer, and Wyeth.

AVR is onSpeaker/AdvisoryBoardsfor,or hasreceived researchfunds from:AstraZeneca, Canadian Network for Mood and Anxiety Treatments, Cephalon,Eli Lilly, GlaxoSmithKline, Janssen-Ortho, Lundbeck, Pzer, Roche, Servier andWyeth.

Acknowledgements

CANMAT thanks the external reviewers: Alain LeSage, MD,FRCPC (University of Montreal), and Jitender Sareen, MD,FRCPC (University of Manitoba).

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Research report

Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinicalguidelines for the management of major depressive disorder in adults.II. Psychotherapy alone or in combination with antidepressant medication

Sagar V. Parikh a , , Zindel V. Segal a , Sophie Grigoriadis a , Arun V. Ravindran a , Sidney H. Kennedy a ,Raymond W. Lam b , Scott B. Patten ca University of Toronto, Canadab University of British Columbia, Canadac University of Calgary, Canada

a r t i c l e i n f o a b s t r a c t


Background : In 2001, the Canadian Psychiatric Association andthe Canadian Network for Moodand Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines forthe treatment of depressive disorders. A revision of these guidelines was undertaken byCANMAT in 2008 2009 to re ect advances in the eld. This article, one of ve in the series,reviews new studies of psychotherapy in the acute and maintenance phase of MDD, includingcomputer-based and telephone-delivered psychotherapy.Methods : The CANMAT guidelines are based on a question answer format to enhanceaccessibility to clinicians. Evidence-based responses are based on updated systematic reviewsof the literatureand recommendationsare gradedaccording to theLevel of Evidence, using pre-de ned criteria. Lines of Treatment are identi ed based on criteria that included evidence andexpert clinical support.Results: Cognitive-Behavioural Therapy (CBT) and Interpersonal Therapy (IPT) continue to havethe most evidence for ef cacy, both in acute and maintenance phases of MDD, and have beenstudied in combination with antidepressants. CBT is well studied in conjunction withcomputer-delivered methods and bibliotherapy. Behavioural Activation and Cognitive-Behavioural Analysis System of Psychotherapy have signi cant evidence, but needreplication. Newer psychotherapies including Acceptance and Commitment Therapy,Motivational Interviewing, and Mindfulness-Based Cognitive Therapy do not yet havesigni cant evidence as acute treatments; nor does psychodynamic therapy.Limitations : Although many forms of psychotherapy have been studied, relatively few typeshave been evaluated for MDD in randomized controlled trials. Evidence about the combinationof different types of psychotherapy and antidepressant medication is also limited despitewidespread use of these therapies concomitantly.Conclusions : CBTand IPTare the only rst-line treatment recommendations for acute MDD andremain highly recommended for maintenance. Both computer-based and telephone-deliveredpsychotherapy primarily studied with CBT and IPT are useful second-line recommendations.Where feasible, combined antidepressant and CBT or IPT are recommended as rst-linetreatments for acute MDD.

2009 Published by Elsevier B.V.

Keywords:Canadian Network for Mood and AnxietyTreatments (CANMAT)Major depressive disorder

Antidepressant medicationCognitive-behavioural therapyInterpersonal therapyDepression focused psychotherapyPsychodynamic therapyInternet psychotherapyTelephone psychotherapyBehavioural activationCombined treatment

Introduction

The Canadian Psychiatric Association and the CanadianNetwork for Mood and Anxiety Treatments (CANMAT), a not-for-pro t scienti c and educational organization, collaborated


Corresponding author.E-mail addresses: [email protected] (S.V. Parikh).

0165-0327/$






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on the publication in 2001 of evidence-based clinical guide-lines for the treatment of depressive disorders ( Kennedy andLam, 2001 ). A revision of these guidelines was undertaken byCANMAT in 2008 2009 to update the recommendationsbased on new evidence. The scope of these guidelinesencompasses the management of adults with unipolar majordepressive disorder (MDD). This section reviews psychother-apy, alone and in combination with medication, while a seriesof 4 companion sections review other aspects of MDD. Thereareseparate CANMAT guidelines for Bipolar Disorder ( Yathamet al., 2009 ).

Psychotherapy refers to the treatment of psychiatric andbehavioural disorders through a method of communicatingthat invokes a psychological model of illness. This method of communication begins with a patient whoseeks alleviation of current symptoms or prevention of recurrence of symptoms.Historically this required the establishment of a professionalrelationship between a patient and a therapist; with theadvent of computer, internet, self-help, and to a lesser extenttelephone therapies, the relationship is more explicitlybetween the patient and the psychological model, with animplicit link to the therapist who designed the therapy.

Psychotherapy predates somatic therapies and includes ahost of models, several of which have been rigorously tested,speci cally for MDD. This review summarizes depression-speci c psychotherapies as well as newer therapies which arepromising, and seeks to clarify the evidence and usefulness of each major psychotherapy. Whilemost psychotherapies sharemany common elements, the major treatments for MDD maybe characterized by a number of key components: (a) the goalof treatment is alleviation of the core symptoms of depres-sion, (b) there is careful attention to a speci c method todeliver the therapy (typically a manual), (c) the psychother-

apy focuses on the current problems of the patient, (d) highlevels of activity are expected both of the therapist and thepatient (who frequently has homework ), (e) careful symp-tom monitoring, preferably with rating scales, is expected, (f)psychoeducation about the illness is a universal component,and (g) the treatment is generally time-limited, oftenparalleling the time course for pharmacotherapy. Further-more, many of these therapies have been modi ed to bedelivered in a group format. While a group approach mayallow for integration of new techniques involving peerfeedback and may be more cost-effective, the core of thepsychotherapy remains unchanged, so group interventionsare not evaluated in these guidelines as a separate group

therapy

. Similarly, context-speci c therapies (such as mar-ital therapy forMDDcoinciding with a severemarital dispute)are not evaluated, since such therapies do not generalize tothe average person with depression. Indications for a speci ctherapy, and the choice of either psychotherapy or pharma-cotherapy alone or in combination are reviewed in a numberof the following questions. The recommendations are pre-sentedas guidance for clinicians whoshouldconsider them inthe context of individual patients, and not as standards of care.

Methods

Thefull methods have been describedelsewhere ( Kennedyet al., 2009 ) but, in summary, relevant English language

publications from January 1, 2000 to December 31, 2008 wereidenti ed using computerized searches of electronic data-bases (PubMed, PsychInfo, Cochrane Register of ClinicalTrials), inspection of bibliographies, and review of otherguidelines and major reports. The previous question answerformat has been retained based on feedback from clinicians.Recommendations for each Line ofTreatment arebasedon theLevel of Evidence and clinical support ( Table 1 ). A rst-linetreatment represents a balance of ef cacy, tolerability andclinical support. Second-line and third-line treatments arereserved for situations where rst-line treatments are notindicated or cannot be used, or have not worked.

CANMAT recognizes that much of the evidence is based onstudies using strict inclusion/exclusion criteria with intensiveand frequent follow up for a short duration of treatment, andtherefore maynotbe applicable to the average patient seen byclinicians. Hence, there are few absolute recommendationsand these guidelines should be viewed as guidance that mustbe tailored to an individual patient, and not as standards of care.

2.1. When is psychotherapy indicated for treatment?

Many factors in uence the decision of when and where toemploy psychotherapy. Employing a broad perspective, thereare patient, provider, and (health) system issues that eachplay a role. Among the patient factors are adequacy of clinicalevidence for a speci c patient population (e.g. women duringpregnancy); medication contraindications; patient prefer-ence; and the ability of a patient to engage in treatment.Patient preferences may in turn be in uenced by social orcultural convictions regarding the ef cacy of particular non-medical therapies, and the fear of potential medication side

Table 1Criteria for level of evidence a and line of treatment b .

Level Criteria

1 At least 2 RCTs with adequate sample sizes, preferably placebo-controlled, and/or meta-analysis with narrow con dence intervals.

2 At least 1 RCT with adequate sample size and/or meta-analysis withwide con dence intervals.

3 Non-randomized, controlled prospective studies or case series orhighquality retrospective studies.


Line of treatment Criteria

First-line Level 1 or Level 2 evidence, plus clinical support c

Second-line Level 3 evidence or higher, plus clinical support c

Third-line Level 4 evidence or higher, plus clinical support ca Note that Levels 1 and 2 evidence refer speci cally to treatment studies

in which randomized comparisons are available. Recommendations invol-ving epidemiological or risk factors primarily arise from observationalstudies, hence the highest level of evidence is usually Level 3. Higher orderrecommendations (e.g., principles of care) re ect higher level judgment of the strength of evidence from various data sources, and therefore areprimarily Level 4 evidence.

b A rst-line treatment represents a balance of ef cacy, tolerability andclinical support. Second-line and third-line treatments are reserved forsituations where rst-line treatments are not indicated or cannot be used, orwhen rst-line treatments have not worked.

c Clinical support refers to application of expert opinion of the CANMATcommittees to ensure that evidence-supported interventions are realistic inclinical practice. Therefore, treatments with higher levels of evidence may be

downgraded to lower lines of treatment due to clinical issues such as sideeffect or safety pro le.

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effects. Provider factors include the ability to provide thechosen psychotherapy of suf cient quality and in suf cientquantity to meet patient needs, as well as the capacity toengage the patient. System factors include ease of availabilityand if applicable, cost. System factors also playa role in whichtherapies are provided: some systems provide paid coveragefor traditional psychotherapies such as psychodynamicmethods for historical reasons, while other systems facilitatetreatments that can be provided by speci c professionalgroups within the health care system for instance, theprovision of CBT by specially trained counselors.

For the clinician using these guidelines, it would bereasonable to begin by identifying the rst-line psychologicaltreatments recommended for MDD, clarifying if there are anyparticular recommendations for a special subpopulation, andevaluating how the evidence and availability for thesetreatments compare to the evidence and availability of somatic therapies. Severity is another overarching issue inconsidering whether to recommend psychotherapy: for themost severe depressions, the ef cacy and speed of somatictherapy over psychotherapy is a consideration.

Safety and relative contraindications should also be con-sidered; it would be unwise to recommend monotherapy withpsychotherapy in a severely suicidal patient, and the presenceof psychotic depression would be an instance where psy-chotherapy alonewould be contraindicated. While it is intuitiveto assume that the combination of psychotherapy andpharmacotherapy may be better than either treatment alone,thestrength of evidence variesacross therapie

Documents

CANMAT Depression Guidelines 2009.PDF